Delivery of compounds for the treatment of Parkinsons through an inhalation route

ABSTRACT

The present invention relates to the delivery of antiparkinsons drugs through an inhalation route. In a method aspect of the present invention, an antiparkinsons drug is administered to a patient through an inhalation route. The method comprises: a) heating a thin layer of an antiparkinsons drug on a solid support to form a vapor; and, b) passing air through the heated vapor to produce aerosol particles having less than 5% drug degradation products. In a kit aspect of the present invention, a kit for delivering an antiparkinsons drug through an inhalation route is provided which comprises: a) a thin coating of a an antiparkinsons drug composition; and, b) a device for dispending said thin coating as a condensation aerosol.

[0001] This application is a continuation of U.S. patent applicationSer. No. 10/153,139, entitled “Delivery of Compounds for the Treatmentof Parkinsons Through an Inhalation Route,” filed May 20, 2002,Rabinowitz and Zaffaroni; which claims priority to U.S. provisionalapplication Ser. No. 60/294,203 entitled “Thermal Vapor Delivery ofDrugs,” filed May 24, 2001, Rabinowitz and Zaffaroni, the entiredisclosure of which is hereby incorporated by reference. Thisapplication further claims priority to U.S. provisional application Ser.No. 60/317,479 entitled “Aerosol Drug Delivery,” filed Sep. 5, 2001,Rabinowitz and Zaffaroni, the entire disclosure of which is herebyincorporated by reference.

FIELD OF THE INVENTION

[0002] The present invention relates to the delivery of compounds forthe treatment of Parkinsons through an inhalation route. Specifically,it relates to aerosols containing antiparkinsonian drugs that are usedin inhalation therapy.

BACKGROUND OF THE INVENTION

[0003] There are a number of compositions currently marketed for thetreatment of Parkinsons. The compositions contain at least one activeingredient that provides for observed therapeutic effects. Among theactive ingredients given in such antiparkinsoniam compositions arebenzotropine, pergolide, ropinerole, amantadine and deprenyl.

[0004] It is desirable to provide a new route of administration forantiparkinsonian drugs that rapidly produces peak plasma concentrationsof the compounds. The provision of such a route is an object of thepresent invention.

SUMMARY OF THE INVENTION

[0005] The present invention relates to the delivery of compounds forthe treatment of Parkinsons through an inhalation route. Specifically,it relates to aerosols containing antiparkinsonian drugs that are usedin inhalation therapy.

[0006] In a composition aspect of the present invention, the aerosolcomprises particles comprising at least 5 percent by weight of anantiparkinsonian drug. Preferably, the particles comprise at least 10percent by weight of an antiparkinsonian drug. More preferably, theparticles comprise at least 20 percent, 30 percent, 40 percent, 50percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97percent, 99 percent, 99.5 percent or 99.97 percent by weight of anantiparkinsonian drug.

[0007] Typically, the aerosol has a mass of at least 10 μg. Preferably,the aerosol has a mass of at least 100 μg. More preferably, the aerosolhas a mass of at least 0.200 μg.

[0008] Typically, the particles comprise less than 10 percent by weightof antiparkinsonian drug degradation products. Preferably, the particlescomprise less than 5 percent by weight of antiparkinsonian drugdegradation products. More preferably, the particles comprise less than2.5, 1, 0.5, 0.1 or 0.03 percent by weight of antiparkinsonian drugdegradation products.

[0009] Typically, the particles comprise less than 90 percent by weightof water. Preferably, the particles comprise less than 80 percent byweight of water. More preferably, the particles comprise less than 70percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10percent, or 5 percent by weight of water.

[0010] Typically, at least 50 percent by weight of the aerosol isamorphous in form, wherein crystalline forms make up less than 50percent by weight of the total aerosol weight, regardless of the natureof individual particles. Preferably, at least 75 percent by weight ofthe aerosol is amorphous in form. More preferably, at least 90 percentby weight of the aerosol is amorphous in form.

[0011] Typically, the aerosol has an inhalable aerosol particle densitygreater than 10⁶ particles/mL. Preferably, the aerosol has an inhalableaerosol particle density greater than 10⁷ particles/mL or 10⁸particles/mL.

[0012] Typically, the aerosol particles have a mass median aerodynamicdiameter of less than 5 microns. Preferably, the particles have a massmedian aerodynamic diameter of less than 3 microns. More preferably, theparticles have a mass median aerodynamic diameter of less than 2 or 1micron(s).

[0013] Typically, the geometric standard deviation around the massmedian aerodynamic diameter of the aerosol particles is less than 3.0.Preferably, the geometric standard deviation is less than 2.5. Morepreferably, the geometric standard deviation is less than 2.3.

[0014] Typically, the aerosol is formed by heating a compositioncontaining an antiparkinsonian drug to form a vapor and subsequentlyallowing the vapor to condense into an aerosol.

[0015] In another composition aspect of the present invention, theaerosol comprises particles comprising at least 5 percent by weight ofbenzotropine, pergolide, ropinerole, amantadine or deprenyl. Preferably,the particles comprise at least 10 percent by weight of benzotropine,pergolide, ropinerole, amantadine or deprenyl. More preferably, theparticles comprise at least 20 percent, 30 percent, 40 percent, 50percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97percent, 99 percent, 99.5 percent or 99.97 percent by weight ofbenzotropine, pergolide, ropinerole, amantadine or deprenyl.

[0016] Typically, the aerosol has a mass of at least 10 μg. Preferably,the aerosol has a mass of at least 100 μg. More preferably, the aerosolhas a mass of at least 200 μg.

[0017] Typically, the particles comprise less than 10 percent by weightof benzotropine, pergolide, ropinerole, amantadine or deprenyldegradation products. Preferably, the particles comprise less than 5percent by weight of benzotropine, pergolide, ropinerole, amantadine ordeprenyl degradation products. More preferably, the particles compriseless than 2.5, 1, 0.5, 0.1 or 0.03 percent by weight of benzotropine,pergolide, ropinerole, amantadine or deprenyl degradation products.

[0018] Typically, the particles comprise less than 90 percent by weightof water. Preferably, the particles comprise less than 80 percent byweight of water. More preferably, the particles comprise less than 70percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10percent, or 5 percent by weight of water.

[0019] Typically, at least 50 percent by weight of the aerosol isamorphous in form, wherein crystalline forms make up less than 50percent by weight of the total aerosol weight, regardless of the natureof individual particles. Preferably, at least 75 percent by weight ofthe aerosol is amorphous in form. More preferably, at least 90 percentby weight of the aerosol is amorphous in form.

[0020] Typically, where the aerosol comprises benzotropine, the aerosolhas an inhalable aerosol drug mass density of between 0.1 mg/L and 4mg/L. Preferably, the aerosol has an inhalable aerosol drug mass densityof between 0.2 mg/L and 3 mg/L. More preferably, the aerosol has aninhalable aerosol drug mass density of between 0.3 mg/L and 2 mg/L.

[0021] Typically, where the aerosol comprises pergolide, the aerosol hasan inhalable aerosol drug mass density of between 0.01 mg/L and 2.5mg/L. Preferably, the aerosol has an inhalable aerosol drug mass densityof between 0.02 mg/L and 1 mg/L. More preferably, the aerosol has aninhalable aerosol drug mass density of between 0.05 mg/L and 0.5 mg/L.

[0022] Typically, where the aerosol comprises ropinerole, the aerosolhas an inhalable aerosol drug mass density of between 0.02 mg/L and 4mg/L. Preferably, the aerosol has an inhalable aerosol drug mass densityof between 0.04 mg/L and 2 mg/L. More preferably, the aerosol has aninhalable aerosol drug mass density of between 0.10 mg/L and 1.0 mg/L.

[0023] Typically, where the aerosol comprises amantadine, the aerosolhas an inhalable aerosol drug mass density of between 5 mg/L and 500mg/L. Preferably, the aerosol has an inhalable aerosol drug mass densityof between 10 mg/L and 200 mg/L. More preferably, the aerosol has aninhalable aerosol drug mass density of between 20 mg/L and 150 mg/L.

[0024] Typically, where the aerosol comprises deprenyl, the aerosol hasan inhalable aerosol drug mass density of between 0.5 mg/L and 12.5mg/L. Preferably, the aerosol has an inhalable aerosol drug mass densityof between 1 mg/L and 10 mg/L. More preferably, the aerosol has aninhalable aerosol drug mass density of between 2 mg/L and 7.5 mg/L.

[0025] Typically, the aerosol has an inhalable aerosol particle densitygreater than 10⁶ particles/mL. Preferably, the aerosol has an inhalableaerosol particle density greater than 10⁷ particles/mL or 10 ⁸particles/mL.

[0026] Typically, the aerosol particles have a mass median aerodynamicdiameter of less than 5 microns. Preferably, the particles have a massmedian aerodynamic diameter of less than 3 microns. More preferably, theparticles have a mass median aerodynamic diameter of less than 2 or 1micron(s).

[0027] Typically, the geometric standard deviation around the massmedian aerodynamic diameter of the aerosol particles is less than 3.0.Preferably, the geometric standard deviation is less than 2.5. Morepreferably, the geometric standard deviation is less than 2.3.

[0028] Typically, the aerosol is formed by heating a compositioncontaining benzotropine, pergolide, ropinerole, amantadine or deprenylto form a vapor and subsequently allowing the vapor to condense into anaerosol.

[0029] In a method aspect of the present invention, an antiparkinsoniandrug is delivered to a mammal through an inhalation route. The methodcomprises: a) heating a composition, wherein the composition comprisesat least 5 percent by weight of an antiparkinsonian drug, to form avapor; and, b) allowing the vapor to cool, thereby forming acondensation aerosol comprising particles, which is inhaled by themammal. Preferably, the composition that is heated comprises at least 10percent by weight of an antiparkinsonian drug. More preferably, thecomposition comprises at least 20 percent, 30 percent, 40 percent, 50percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent byweight of an antiparkinsonian drug.

[0030] Typically, the particles comprise at least 5 percent by weight ofan antiparkinsonian drug. Preferably, the particles comprise at least 10percent by weight of an antiparkinsonian drug. More preferably, theparticles comprise at least 20 percent, 30 percent, 40 percent, 50percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent byweight of an antiparkinsonian drug.

[0031] Typically, the condensation aerosol has a mass of at least 10 μg.Preferably, the aerosol has a mass of at least 100 μg. More preferably,the aerosol has a mass of at least 200μ.

[0032] Typically, the particles comprise less than 10 percent by weightof antiparkinsonian drug degradation products. Preferably, the particlescomprise less than 5 percent by weight of antiparkinsonian drugdegradation products. More preferably, the particles comprise 2.5, 1,0.5, 0.1 or 0.03 percent by weight of antiparkinsonian drug degradationproducts.

[0033] Typically, the particles comprise less than 90 percent by weightof water. Preferably, the particles comprise less than 80 percent byweight of water. More preferably, the particles comprise less than 70percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10percent, or 5 percent by weight of water.

[0034] Typically, at least 50 percent by weight of the aerosol isamorphous in form, wherein crystalline forms make up less than 50percent by weight of the total aerosol weight, regardless of the natureof individual particles. Preferably, at least 75 percent by weight ofthe aerosol is amorphous in form. More preferably, at least 90 percentby weight of the aerosol is amorphous in form.

[0035] Typically, the particles of the delivered condensation aerosolhave a mass median aerodynamic diameter of less than 5 microns.Preferably, the particles have a mass median aerodynamic diameter ofless than 3 microns. More preferably, the particles have a mass medianaerodynamic diameter of less than 2 or 1 micron(s).

[0036] Typically, the geometric standard deviation around the massmedian aerodynamic diameter of the aerosol particles is less than 3.0.Preferably, the geometric standard deviation is less than 2.5. Morepreferably, the geometric standard deviation is less than 2.3.

[0037] Typically, the delivered aerosol has an inhalable aerosolparticle density greater than 10⁶ particles/mL. Preferably, the aerosolhas an inhalable aerosol particle density greater than 10⁷ particles/mLor 10 ⁸ particles/mL.

[0038] Typically, the rate of inhalable aerosol particle formation ofthe delivered condensation aerosol is greater than 10⁸ particles persecond. Preferably, the aerosol is formed at a rate greater than 10⁹inhalable particles per second. More preferably, the aerosol is formedat a rate greater than 10¹⁰ inhalable particles per second.

[0039] Typically, the delivered condensation aerosol is formed at a rategreater than 0.5 mg/second. Preferably, the aerosol is formed at a rategreater than 0.75 mg/second. More preferably, the aerosol is formed at arate greater than 1 mg/second, 1.5 mg/second or 2 mg/second.

[0040] Typically, the delivered condensation aerosol results in a peakplasma concentration of an antiparkinsonian drug in the mammal in lessthan 1 h. Preferably, the peak plasma concentration is reached in lessthan 0.5 h. More preferably, the peak plasma concentration is reached inless than 0.2, 0.1, 0.05, 0.02, 0.01, or 0.005 h (arterial measurement).

[0041] In another method aspect of the present invention, one ofbenzotropine, pergolide, ropinerole, amantadine or deprenyl is deliveredto a mammal through an inhalation route. The method comprises: a)heating a composition, wherein the composition comprises at least 5percent by weight of benzotropine, pergolide, ropinerole, amantadine ordeprenyl, to form a vapor; and, b) allowing the vapor to cool, therebyforming a condensation aerosol comprising particles, which is inhaled bythe mammal. Preferably, the composition that is heated comprises atleast 10 percent by weight of benzotropine, pergolide, ropinerole,amantadine or deprenyl. More preferably, the composition comprises atleast 20 percent, 30 percent, 40 percent, 50 percent, 60 percent, 70percent, 80 percent, 90 percent, 95 percent, 97 percent, 99 percent,99.5 percent, 99.9 percent or 99.97 percent by weight of benzotropine,pergolide, ropinerole, amantadine or deprenyl.

[0042] Typically, the particles comprise at least 5 percent by weight ofbenzotropine, pergolide, ropinerole, amantadine or deprenyl. Preferably,the particles comprise at least 10 percent by weight of benzotropine,pergolide, ropinerole, amantadine or deprenyl. More preferably, theparticles comprise at least 20 percent, 30 percent, 40 percent, 50percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent, 97percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent byweight of benzotropine, pergolide, ropinerole, amantadine or deprenyl.

[0043] Typically, the condensation aerosol has a mass of at least 10 μg.Preferably, the aerosol has a mass of at least 100 μg. More preferably,the aerosol has a mass of at least 200 μg.

[0044] Typically, the particles comprise less than 10 percent by weightof benzotropine, pergolide, ropinerole, amantadine or deprenyldegradation products. Preferably, the particles comprise less than 5percent by weight of benzotropine, pergolide, ropinerole, amantadine ordeprenyl degradation products. More preferably, the particles comprise2.5, 1, 0.5, 0.1 or 0.03 percent by weight of benzotropine, pergolide,ropinerole, amantadine or deprenyl degradation products.

[0045] Typically, the particles comprise less than 90 percent by weightof water. Preferably, the particles comprise less than 80 percent byweight of water. More preferably, the particles comprise less than 70percent, 60 percent, 50 percent, 40 percent, 30 percent, 20 percent, 10percent, or 5 percent by weight of water.

[0046] Typically, at least 50 percent by weight of the aerosol isamorphous in form, wherein crystalline forms make up less than 50percent by weight of the total aerosol weight, regardless of the natureof individual particles. Preferably, at least 75 percent by weight ofthe aerosol is amorphous in form. More preferably, at least 90 percentby weight of the aerosol is amorphous in form.

[0047] Typically, the particles of the delivered condensation aerosolhave a mass median aerodynamic diameter of less than 5 microns.Preferably, the particles have a mass median aerodynamic diameter ofless than 3 microns. More preferably, the particles have a mass medianaerodynamic diameter of less than 2 or 1 micron(s).

[0048] Typically, the geometric standard deviation around the massmedian aerodynamic diameter of the aerosol particles is less than 3.0.Preferably, the geometric standard deviation is less than 2.5. Morepreferably, the geometric standard deviation is less than 2.3.

[0049] Typically, where the aerosol comprises benzotropine, thedelivered aerosol has an inhalable aerosol drug mass density of between0.1 mg/L and 4 mg/L. Preferably, the aerosol has an inhalable aerosoldrug mass density of between 0.2 mg/L and 3 mg/L. More preferably, theaerosol has an inhalable aerosol drug mass density of between 0.3 mg/Land 2 mg/L.

[0050] Typically, where the aerosol comprises pergolide, the deliveredaerosol has an inhalable aerosol drug mass density of between 0.01 mg/Land 2.5 mg/L. Preferably, the aerosol has an inhalable aerosol drug massdensity of between 0.02 mg/L and 1 mg/L. More preferably, the aerosolhas an inhalable aerosol drug mass density of between 0.05 mg/L and 0.5mg/L.

[0051] Typically, where the aerosol comprises ropinerole, the deliveredaerosol has an inhalable aerosol drug mass density of between 0.02 mg/Land 4 mg/L. Preferably, the aerosol has an inhalable aerosol drug massdensity of between 0.04 mg/L and 2 mg/L. More preferably, the aerosolhas an inhalable aerosol drug mass density of between 0.10 mg/L and 1.0mg/L.

[0052] Typically, where the aerosol comprises amantadine, the deliveredaerosol has an inhalable aerosol drug mass density of between 5 mg/L and500 mg/L. Preferably, the aerosol has an inhalable aerosol drug massdensity of between 10 mg/L and 200 mg/L. More preferably, the aerosolhas an inhalable aerosol drug mass density of between 20 mg/L and 150mg/L.

[0053] Typically, where the aerosol comprises deprenyl, the deliveredaerosol has an inhalable aerosol drug mass density of between 0.5 mg/Land 12.5 mg/L. Preferably, the aerosol has an inhalable aerosol drugmass density of between 1 mg/L and 10 mg/L. More preferably, the aerosolhas an inhalable aerosol drug mass density of between 2 mg/L and 7.5mg/L.

[0054] Typically, the delivered aerosol has an inhalable aerosolparticle density greater than 10⁶ particles/mL. Preferably, the aerosolhas an inhalable aerosol particle density greater than 10⁷ particles/mLor 10⁸ particles/mL.

[0055] Typically, the rate of inhalable aerosol particle formation ofthe delivered condensation aerosol is greater than 10⁸ particles persecond. Preferably, the aerosol is formed at a rate greater than 10⁹inhalable particles per second. More preferably, the aerosol is formedat a rate greater than 10¹⁰ inhalable particles per second.

[0056] Typically, the delivered condensation aerosol is formed at a rategreater than 0.5 mg/second. Preferably, the aerosol is formed at a rategreater than 0.75 mg/second. More preferably, the aerosol is formed at arate greater than 1 mg/second, 1.5 mg/second or 2 mg/second.

[0057] Typically, where the condensation aerosol comprises benzotropine,between 0.1 mg and 4 mg of benzotropine are delivered to the mammal in asingle inspiration. Preferably, between 0.2 mg and 3 mg of benzotropineare delivered to the mammal in a single inspiration. More preferably,between 0.3 mg and 2 mg of benzotropine are delivered to the mammal in asingle inspiration.

[0058] Typically, where the condensation aerosol comprises pergolide,between 0.01 mg and 2.5 mg of pergolide are delivered to the mammal in asingle inspiration. Preferably, between 0.02 mg and 1 mg of pergolideare delivered to the mammal in a single inspiration. More preferably,between 0.05 mg and 0.5 mg of pergolide are delivered to the mammal in asingle inspiration.

[0059] Typically, where the condensation aerosol comprises ropinerole,between 0.02 mg and 4 mg of ropinerole are delivered to the mammal in asingle inspiration. Preferably, between 0.04 mg and 2 mg of ropineroleare delivered to the mammal in a single inspiration. More preferably,between 0.1 mg and 1.0 mg of ropinerole are delivered to the mammal in asingle inspiration.

[0060] Typically, where the condensation aerosol comprises amantadine,between 5 mg and 500 mg of amantadine are delivered to the mammal in asingle inspiration. Preferably, between 10 mg and 200 mg of amantadineare delivered to the mammal in a single inspiration. More preferably,between 20 mg and 150 mg of amantadine are delivered to the mammal in asingle inspiration.

[0061] Typically, where the condensation aerosol comprises deprenyl,between 0.5 mg and 12.5 mg of deprenyl are delivered to the mammal in asingle inspiration. Preferably, between 1 mg and 10 mg of deprenyl aredelivered to the mammal in a single inspiration. More preferably,between 2 mg and 7.5 mg of deprenyl are delivered to the mammal in asingle inspiration.

[0062] Typically, the delivered condensation aerosol results in a peakplasma concentration of benzotropine, pergolide, ropinerole, amantadineor deprenyl in the mammal in less than 1 h. Preferably, the peak plasmaconcentration is reached in less than 0.5 h. More preferably, the peakplasma concentration is reached in less than 0.2, 0.1, 0.05, 0.02, 0.01,or 0.005 h (arterial measurement).

[0063] In a kit aspect of the present invention, a kit for delivering anantiparkinsonian through an inhalation route to a mammal is providedwhich comprises: a) a composition comprising at least 5 percent byweight of an antiparkinsonian drug; and, b) a device that forms anantiparkinsonian drug aerosol from the composition, for inhalation bythe mammal. Preferably, the composition comprises at least 20 percent,30 percent, 40 percent, 50 percent, 60 percent, 70 percent, 80 percent,90 percent, 95 percent, 97 percent, 99 percent, 99.5 percent, 99.9percent or 99.97 percent by weight of an antiparkinsonian drug.

[0064] Typically, the device contained in the kit comprises: a) anelement for heating the antiparkinsonian drug composition to form avapor; b) an element allowing the vapor to cool to form an aerosol; and,c) an element permitting the mammal to inhale the aerosol.

[0065] In another kit aspect of the present invention, a kit fordelivering benzotropine, pergolide, ropinerole, amantadine or deprenylthrough an inhalation route to a mammal is provided which comprises: a)a composition comprising at least 5 percent by weight of benzotropine,pergolide, ropinerole, amantadine or deprenyl; and, b) a device thatforms a benzotropine, pergolide, ropinerole, amantadine or deprenylaerosol from the composition, for inhalation by the mammal. Preferably,the composition comprises at least 20 percent, 30 percent, 40 percent,50 percent, 60 percent, 70 percent, 80 percent, 90 percent, 95 percent,97 percent, 99 percent, 99.5 percent, 99.9 percent or 99.97 percent byweight of benzotropine, pergolide, ropinerole, amantadine or deprenyl.

[0066] Typically, the device contained in the kit comprises: a) anelement for heating the benzotropine, pergolide, ropinerole, amantadineor deprenyl composition to form a vapor; b) an element allowing thevapor to cool to form an aerosol; and, c) an element permitting themammal to inhale the aerosol.

BRIEF DESCRIPTION OF THE FIGURE

[0067]FIG. 1 shows a cross-sectional view of a device used to deliverantiparkinsonian drug aerosols to a mammal through an inhalation route.

DETAILED DESCRIPTION OF THE INVENTION

[0068] Definitions

[0069] “Aerodynamic diameter” of a given particle refers to the diameterof a spherical droplet with a density of 1 g/mL (the density of water)that has the same settling velocity as the given particle.

[0070] “Aerosol” refers to a suspension of solid or liquid particles ina gas.

[0071] “Aerosol drug mass density” refers to the mass of anantiparkinsonian drug per unit volume of aerosol.

[0072] “Aerosol mass density” refers to the mass of particulate matterper unit volume of aerosol.

[0073] “Aerosol particle density” refers to the number of particles perunit volume of aerosol.

[0074] “Amantadine” refers to tricylo[3.3.1.1^(3,7)]decan-1-amine.

[0075] “Amantadine degradation product” refers to a compound resultingfrom a chemical modification of amantadine. The modification, forexample, can be the result of a thermally or photochemically inducedreaction. Such reactions include, without limitation, oxidation andhydrolysis. An example of a degradation product is nitroso-adamantane.

[0076] “Amorphous particle” refers to a particle that does not containmore than 50 percent by weight of a crystalline form. Preferably, theparticle does not contain more than 25 percent by weight of acrystalline form. More preferably, the particle does not contain morethan 10 percent by weight of a crystalline form.

[0077] “Antiparkinsonian drug degradation product” refers to a compoundresulting from a chemical modification of an antiparkinsonian drug. Themodification, for example, can be the result of a thermally orphotochemically induced reaction. Such reactions include, withoutlimitation, oxidation and hydrolysis.

[0078] “Benzotropine” refers to3-(diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]-octane.

[0079] “Benzotropine degradation product” refers to a compound resultingfrom a chemical modification of benzotropine. The modification, forexample, can be the result of a thermally or photochemically inducedreaction. Such reactions include, without limitation, oxidation andhydrolysis.

[0080] “Condensation aerosol” refers to an aerosol formed byvaporization of a substance followed by condensation of the substanceinto an aerosol.

[0081] “Deprenyl” refers to {circle over(R)}-(−)-N,2-dimethyl-N-2-propynylphenethylamine.

[0082] “Deprenyl degradation product” refers to a compound resultingfrom a chemical modification of deprenyl. The modification, for example,can be the result of a thermally or photochemically induced reaction.Such reactions include, without limitation, oxidation and hydrolysis.

[0083] “Inhalable aerosol drug mass density” refers to the aerosol drugmass density produced by an inhalation device and delivered into atypical patient tidal volume.

[0084] “Inhalable aerosol mass density” refers to the aerosol massdensity produced by an inhalation device and delivered into a typicalpatient tidal volume.

[0085] “Inhalable aerosol particle density” refers to the aerosolparticle density of particles of size between 100 nm and 5 micronsproduced by an inhalation device and delivered into a typical patienttidal volume.

[0086] “Mass median aerodynamic diameter” or “MMAD” of an aerosol refersto the aerodynamic diameter for which half the particulate mass of theaerosol is contributed by particles with an aerodynamic diameter largerthan the MMAD and half by particles with an aerodynamic diameter smallerthan the MMAD.

[0087] “Pergolide” refers to 8-[(methylthio)methyl]-6-propylergoline.

[0088] “Pergolide degradation product” refers to a compound resultingfrom a chemical modification of pergolide. The modification, forexample, can be the result of a thermally or photochemically inducedreaction. Such reactions include, without limitation, oxidation andhydrolysis. An example of a degradation product is 3-nitrophthalic acid.

[0089] “Rate of aerosol formation” refers to the mass of aerosolizedparticulate matter produced by an inhalation device per unit time.

[0090] “Rate of inhalable aerosol particle formation” refers to thenumber of particles of size between 100 nm and 5 microns produced by aninhalation device per unit time.

[0091] “Rate of drug aerosol formation” refers to the mass ofaerosolized antiparkinsonian drug produced by an inhalation device perunit time.

[0092] “Ropinerole” refers to4-[2-(dipropylamino)-ethyl]-1,3-dihydro-2H-indol-2-one.

[0093] “Ropinerole degradation product” refers to a compound resultingfrom a chemical modification of ropinerole. The modification, forexample, can be the result of a thermally or photochemically inducedreaction. Such reactions include, without limitation, oxidation andhydrolysis.

[0094] “Settling velocity” refers to the terminal velocity of an aerosolparticle undergoing gravitational settling in air.

[0095] “Typical patient tidal volume” refers to 1 L for an adult patientand 15 mL/kg for a pediatric patient.

[0096] “Vapor” refers to a gas, and “vapor phase” refers to a gas phase.The term “thermal vapor” refers to a vapor phase, aerosol, or mixture ofaerosol-vapor phases, formed preferably by heating.

[0097] Formation of Antiparkinsonian Drug Containing Aerosols

[0098] Any suitable method is used to form the aerosols of the presentinvention. A preferred method, however, involves heating a compositioncomprising an antiparkinsonian drug to form a vapor, followed by coolingof the vapor such that it condenses to provide an antiparkinsonian drugcomprising aerosol (condensation aerosol). The composition is heated inone of four forms: as pure active compound (e.g., pure benzotropine,pergolide, ropinerole, amantadine or deprenyl); as a mixture of activecompound and a pharmaceutically acceptable excipient; as a salt form ofthe pure active compound; and, as a mixture of active compound salt formand a pharmaceutically acceptable excipient.

[0099] Salt forms of antiparkinsonian drugs (e.g., benzotropine,pergolide, ropinerole, amantadine or deprenyl) are either commerciallyavailable or are obtained from the corresponding free base using wellknown methods in the art. A variety of pharmaceutically acceptable saltsare suitable for aerosolization. Such salts include, without limitation,the following: hydrochloric acid, hydrobromic acid, acetic acid, maleicacid, formic acid, and fumaric acid salts.

[0100] Pharmaceutically acceptable excipients may be volatile ornonvolatile. Volatile excipients, when heated, are concurrentlyvolatilized, aerosolized and inhaled with the antiparkinsonian drug.Classes of such excipients are known in the art and include, withoutlimitation, gaseous, supercritical fluid, liquid and solid solvents. Thefollowing is a list of exemplary carriers within the classes: water;terpenes, such as menthol; alcohols, such as ethanol, propylene glycol,glycerol and other similar alcohols; dimethylformamide;dimethylacetamide; wax; supercritical carbon dioxide; dry ice; andmixtures thereof.

[0101] Solid supports on which the composition is heated are of avariety of shapes. Examples of such shapes include, without limitation,cylinders of less than 1.0 mm in diameter, boxes of less than 1.0 mmthickness and virtually any shape permeated by small (e.g., less than1.0 mm-sized) pores. Preferably, solid supports provide a large surfaceto volume ratio (e.g., greater than 100 per meter) and a large surfaceto mass ratio (e.g., greater than 1 cm² per gram).

[0102] A solid support of one shape can also be transformed into anothershape with different properties. For example, a flat sheet of 0.25 mmthickness has a surface to volume ratio of approximately 8,000 permeter. Rolling the sheet into a hollow cylinder of 1 cm diameterproduces a support that retains the high surface to mass ratio of theoriginal sheet but has a lower surface to volume ratio (about 400 permeter).

[0103] A number of different materials are used to construct the solidsupports. Classes of such materials include, without limitation, metals,inorganic materials, carbonaceous materials and polymers. The followingare examples of the material classes: aluminum, silver, gold, stainlesssteel, copper and tungsten; silica, glass, silicon and alumina;graphite, porous carbons, carbon yarns and carbon felts;polytetrafluoroethylene and polyethylene glycol. Combinations ofmaterials and coated variants of materials are used as well.

[0104] Where aluminum is used as a solid support, aluminum foil is asuitable material. Examples of silica, alumina and silicon basedmaterials include amphorous silica S-5631 (Sigma, St. Louis, Mo.),BCR171 (an alumina of defined surface area greater than 2 m²/g fromAldrich, St. Louis, Mo.) and a silicon wafer as used in thesemiconductor industry. Carbon yarns and felts are available fromAmerican Kynol, Inc., New York, N.Y. Chromatography resins such asoctadecycl silane chemically bonded to porous silica are exemplarycoated variants of silica.

[0105] The heating of the antiparkinsonian drug compositions isperformed using any suitable method. Examples of methods by which heatcan be generated include the following: passage of current through anelectrical resistance element; absorption of electromagnetic radiation,such as microwave or laser light; and, exothermic chemical reactions,such as exothermic solvation, hydration of pyrophoric materials andoxidation of combustible materials.

[0106] Delivery of Antiparkinsonian Drug Containing Aerosols

[0107] Antiparkinsonian drug containing aerosols of the presentinvention are delivered to a mammal using an inhalation device. Wherethe aerosol is a condensation aerosol, the device has at least threeelements: an element for heating an antiparkinsonian drug containingcomposition to form a vapor; an element allowing the vapor to cool,thereby providing a condensation aerosol; and, an element permitting themammal to inhale the aerosol. Various suitable heating methods aredescribed above. The element that allows cooling is, in it simplestform, an inert passageway linking the heating means to the inhalationmeans. The element permitting inhalation is an aerosol exit portal thatforms a connection between the cooling element and the mammal'srespiratory system.

[0108] One device used to deliver the antiparkinsonian drug containingaerosol is described in reference to FIG. 1. Delivery device 100 has aproximal end 102 and a distal end 104, a heating module 106, a powersource 108, and a mouthpiece 110. An antiparkinsonian drug compositionis deposited on a surface 112 of heating module 106. Upon activation ofa user activated switch 114, power source 108 initiates heating ofheating module 106 (e.g, through ignition of combustible fuel or passageof current through a resistive heating element). The antiparkinsoniandrug composition volatilizes due to the heating of heating module 106and condenses to form a condensation aerosol prior to reaching themouthpiece 110 at the proximal end of the device 102. Air flow travelingfrom the device distal end 104 to the mouthpiece 110 carries thecondensation aerosol to the mouthpiece 110, where it is inhaled by themammal.

[0109] Devices, if desired, contain a variety of components tofacilitate the delivery of antiparkinsonian containing aerosols. Forinstance, the device may include any component known in the art tocontrol the timing of drug aerosolization relative to inhalation (e.g.,breath-actuation), to provide feedback to patients on the rate and/orvolume of inhalation, to prevent excessive use (i.e., “lock-out”feature), to prevent use by unauthorized individuals, and/or to recorddosing histories.

[0110] Dosage of Antiparkinsonian Drug Containing Aerosols

[0111] The dosage amount of antiparkinsonian drugs in aerosol form isgenerally no greater than twice the standard dose of the drug givenorally. For instance, benzotropine, pergolide, ropinerole, amantadineand deprenyl are given orally at strengths of 0.5 mg to 2 mg, 0.05 mg to1.0 mg, 0.25 mg to 4 mg, 50 mg to 100 mg, and 5 mg respectively for thetreatment of Parkinsons. As aerosols, 0.1 mg to 4 mg of benztropine,0.01 mg to 2.5 mg of pergolide, 0.02 mg to 4 mg of ropinerole, 5 mg to250 mg of amantadine, and 0.5 mg to 12.5 mg of deprenyl are generallyprovided per inspiration for the same indication. A typical dosage of anantiparkinsonian drug aerosol is either administered as a singleinhalation or as a series of inhalations taken within an hour or less(dosage equals sum of inhaled amounts). Where the drug is administeredas a series of inhalations, a different amount may be delivered in eachinhalation.

[0112] One can determine the appropriate dose of antiparkinsonian drugcontaining aerosols to treat a particular condition using methods suchas animal experiments and a dose-finding (Phase I/II) clinical trial.One animal experiment involves measuring plasma concentrations of drugin an animal after its exposure to the aerosol. Mammals such as dogs orprimates are typically used in such studies, since their respiratorysystems are similar to that of a human. Initial dose levels for testingin humans is generally less than or equal to the dose in the mammalmodel that resulted in plasma drug levels associated with a therapeuticeffect in humans. Dose escalation in humans is then performed, untileither an optimal therapeutic response is obtained or a dose-limitingtoxicity is encountered.

[0113] Analysis of Antiparkinsonian Drug Containing Aerosols

[0114] Purity of an antiparkinsonian drug containing aerosol isdetermined using a number of methods, examples of which are described inSekine et al., Journal of Forensic Science 32:1271-1280 (1987) andMartin et al., Journal of Analytic Toxicology 13:158-162 (1989). Onemethod involves forming the aerosol in a device through which a gas flow(e.g., air flow) is maintained, generally at a rate between 0.4 and 60L/min. The gas flow carries the aerosol into one or more traps. Afterisolation from the trap, the aerosol is subjected to an analyticaltechnique, such as gas or liquid chromatography, that permits adetermination of composition purity.

[0115] A variety of different traps are used for aerosol collection. Thefollowing list contains examples of such traps: filters; glass wool;impingers; solvent traps, such as dry ice-cooled ethanol, methanol,acetone and dichloromethane traps at various pH values; syringes thatsample the aerosol; empty, low-pressure (e.g., vacuum) containers intowhich the aerosol is drawn; and, empty containers that fully surroundand enclose the aerosol generating device. Where a solid such as glasswool is used, it is typically extracted with a solvent such as ethanol.The solvent extract is subjected to analysis rather than the solid(i.e., glass wool) itself. Where a syringe or container is used, thecontainer is similarly extracted with a solvent.

[0116] The gas or liquid chromatograph discussed above contains adetection system (i.e., detector). Such detection systems are well knownin the art and include, for example, flame ionization, photon absorptionand mass spectrometry detectors. An advantage of a mass spectrometrydetector is that it can be used to determine the structure ofantiparkinsonian drug degradation products.

[0117] Particle size distribution of an antiparkinsonian drug containingaerosol is determined using any suitable method in the art (e.g.,cascade impaction). An Andersen Eight Stage Non-viable Cascade Impactor(Andersen Instruments, Smyrna, Ga.) linked to a furnace tube by a mockthroat (USP throat, Andersen Instruments, Smyrna, Ga.) is one systemused for cascade impaction studies.

[0118] Inhalable aerosol mass density is determined, for example, bydelivering a drug-containing aerosol into a confined chamber via aninhalation device and measuring the mass collected in the chamber.Typically, the aerosol is drawn into the chamber by having a pressuregradient between the device and the chamber, wherein the chamber is atlower pressure than the device. The volume of the chamber shouldapproximate the tidal volume of an inhaling patient.

[0119] Inhalable aerosol drug mass density is determined, for example,by delivering a drug-containing aerosol into a confined chamber via aninhalation device and measuring the amount of active drug compoundcollected in the chamber. Typically, the aerosol is drawn into thechamber by having a pressure gradient between the device and thechamber, wherein the chamber is at lower pressure than the device. Thevolume of the chamber should approximate the tidal volume of an inhalingpatient. The amount of active drug compound collected in the chamber isdetermined by extracting the chamber, conducting chromatographicanalysis of the extract and comparing the results of the chromatographicanalysis to those of a standard containing known amounts of drug.

[0120] Inhalable aerosol particle density is determined, for example, bydelivering aerosol phase drug into a confined chamber via an inhalationdevice and measuring the number of particles of given size collected inthe chamber. The number of particles of a given size may be directlymeasured based on the light-scattering properties of the particles.Alternatively, the number of particles of a given size is determined bymeasuring the mass of particles within the given size range andcalculating the number of particles based on the mass as follows: Totalnumber of particles=Sum (from size range 1 to size range N) of number ofparticles in each size range. Number of particles in a given sizerange=Mass in the size range/Mass of a typical particle in the sizerange. Mass of a typical particle in a given size range=π*D³*φ/6, whereD is a typical particle diameter in the size range (generally, the meanboundary MMADs defining the size range) in microns, φ is the particledensity (in g/mL) and mass is given in units of picograms (g⁻¹²).

[0121] Rate of inhalable aerosol particle formation is determined, forexample, by delivering aerosol phase drug into a confined chamber via aninhalation device. The delivery is for a set period of time (e.g., 3 s),and the number of particles of a given size collected in the chamber isdetermined as outlined above. The rate of particle formation is equal tothe number of 100 nm to 5 micron particles collected divided by theduration of the collection time.

[0122] Rate of aerosol formation is determined, for example, bydelivering aerosol phase drug into a confined chamber via an inhalationdevice. The delivery is for a set period of time (e.g., 3 s), and themass of particulate matter collected is determined by weighing theconfined chamber before and after the delivery of the particulatematter. The rate of aerosol formation is equal to the increase in massin the chamber divided by the duration of the collection time.Alternatively, where a change in mass of the delivery device orcomponent thereof can only occur through release of the aerosol phaseparticulate matter, the mass of particulate matter may be equated withthe mass lost from the device or component during the delivery of theaerosol. In this case, the rate of aerosol formation is equal to thedecrease in mass of the device or component during the delivery eventdivided by the duration of the delivery event.

[0123] Rate of drug aerosol formation is determined, for example, bydelivering an antiparkinsonian drug containing aerosol into a confinedchamber via an inhalation device over a set period of time (e.g., 3 s).Where the aerosol is pure antiparkinsonian drug, the amount of drugcollected in the chamber is measured as described above. The rate ofdrug aerosol formation is equal to the amount of antiparkinsonian drugcollected in the chamber divided by the duration of the collection time.Where the antiparkinsonian drug containing aerosol comprises apharmaceutically acceptable excipient, multiplying the rate of aerosolformation by the percentage of antiparkinsonian drug in the aerosolprovides the rate of drug aerosol formation.

[0124] Utility of Antiparkinsonian Drug Containing Aerosols

[0125] The antiparkinsonian drug containing aerosols of the presentinvention are typically used for the treatment of Parkinsons.

[0126] The following examples are meant to illustrate, rather thanlimit, the present invention.

[0127] Benztropine mesylate, pergolide mesylate and amantadine werepurchased from Sigma (www.sigma-aldrich.com). Deprenyl hydrochloride waspurchased from Sigma RBI (www.sigma-aldrich.com). Ropinerolehydrochloride was purchased as REQUIP® tablets from a pharmacy. Otherantiparkinsonian drugs can be similarly obtained.

EXAMPLE 1 General Procedure for Obtaining Free Base of a Compound Salt

[0128] Approximately 1 g of salt (e.g., mono hydrochloride) is dissolvedin deionized water (˜30 mL). Three equivalents of sodium hydroxide (1 NNaOH_(aq)) is added dropwise to the solution, and the pH is checked toensure it is basic. The aqueous solution is extracted four times withdichloromethane (˜50 mL), and the extracts are combined, dried (Na₂SO₄)and filtered. The filtered organic solution is concentrated using arotary evaporator to provide the desired free base. If necessary,purification of the free base is performed using standard methods suchas chromatography or recrystallization.

EXAMPLE 2 General Procedure for Volatilizing Compounds from Halogen Bulb

[0129] A solution of drug in approximately 120 μL dichloromethane iscoated on a 3.5 cm×7.5 cm piece of aluminum foil (precleaned withacetone). The dichloromethane is allowed to evaporate. The coated foilis wrapped around a 300 watt halogen tube (Feit Electric Company, PicoRivera, Calif.), which is inserted into a glass tube sealed at one endwith a rubber stopper. Running 90 V of alternating current (driven byline power controlled by a variac) through the bulb for 3.5 s (drugcoating of 0.01 mg to 8 mg) or for 5 s (drug coating>8 mg) affordsthermal vapor (including aerosol), which is collected on the glass tubewalls. Reverse-phase HPLC analysis with detection by absorption of 225nm light is used to determine the purity of the aerosol. (When desired,the system is flushed through with argon prior to volatilization.) Toobtain higher purity aerosols, one can coat a lesser amount of drug,yielding a thinner film to heat. A linear decrease in film thickness isassociated with a linear decrease in impurities.

[0130] Table 1, which follows, provides data from drugs volatilizedusing the above-recited general procedure. TABLE 1 Compound AerosolPurity Argon Used Benztropine 98.3%  No 99.5%  Yes Pergolide  98% No 98% Yes Ropinerole >90% Yes Amantadine 100% No 100% Yes Deprenyl 100%No  97% Yes

EXAMPLE 3 Particle Size, Particle Density, and Rate of InhalableParticle Formation of Pergolide Aerosol

[0131] A solution of 1.3 mg pergolide in 100 μL dichloromethane wasspread out in a thin layer on the central portion of a 3.5 cm×7 cm sheetof aluminum foil. The dichloromethane was allowed to evaporate. Thealuminum foil was wrapped around a 300 watt halogen tube, which wasinserted into a T-shaped glass tube. Both of the openings of the tubewere left open and the third opening was connected to a 1 liter, 3-neckglass flask. The glass flask was further connected to a large pistoncapable of drawing 1.1 liters of air through the flask. Alternatingcurrent was run through the halogen bulb by application of 90 V using avariac connected to 110 V line power. Within 1 s, an aerosol appearedand was drawn into the 1 L flask by use of the piston, with collectionof the aerosol terminated after 6 s. The aerosol was analyzed byconnecting the 1 L flask to an eight-stage Andersen non-viable cascadeimpactor. Results are shown in table 1. MMAD of the collected aerosolwas 1.8 microns with a geometric standard deviation of 2.2. Also shownin table 1 is the number of particles collected on the various stages ofthe cascade impactor, given by the mass collected on the stage dividedby the mass of a typical particle trapped on that stage. The mass of asingle particle of diameter D is given by the volume of the particle,πD³/6, multiplied by the density of the drug (taken to be 1 g/cm³). Theinhalable aerosol particle density is the sum of the numbers ofparticles collected on impactor stages 3 to 8 divided by the collectionvolume of 1 L, giving an inhalable aerosol particle density of 6.7×10⁶particles/mL. The rate of inhalable aerosol particle formation is thesum of the numbers of particles collected on impactor stages 3 through 8divided by the formation time of 6 s, giving a rate of inhalable aerosolparticle formation of 1.1×10⁹ particles/second. TABLE 1 Determination ofthe characteristics of a pergolide condensation aerosol by cascadeimpaction using an Andersen 8-stage non-viable cascade impactor run at 1cubic foot per minute air flow. Particle Average Mass Number size rangeparticle size collected of Stage (microns) (microns) (mg) particles 0 9.0-10.0 9.5 0.01 1.3 × 10⁴ 1 5.8-9.0 7.4 0.02 7.5 × 10⁴ 2 4.7-5.8 5.250.03 3.6 × 10⁵ 3 3.3-4.7 4.0 0.06 1.9 × 10⁶ 4 2.1-3.3 2.7 0.10 9.8 × 10⁶5 1.1-2.1 1.6 0.19 8.8 × 10⁷ 6 0.7-1.1 0.9 0.09 2.5 × 10⁸ 7 0.4-0.7 0.550.04 4.0 × 10⁸ 8   0-0.4 0.2 0.03 6.0 × 10⁹

EXAMPLE 4 Drug Mass Density and Rate of Drug Aerosol Formation ofPergolide Aerosol

[0132] A solution of 1.0 mg pergolide in 100 μL dichloromethane wasspread out in a thin layer on the central portion of a 3.5 cm×7 cm sheetof aluminum foil. The dichloromethane was allowed to evaporate. Thealuminum foil was wrapped around a 300 watt halogen tube, which wasinserted into a T-shaped glass tube. Both of the openings of the tubewere left open and the third opening was connected to a 1 liter, 3-neckglass flask. The glass flask was further connected to a large pistoncapable of drawing 1.1 liters of air through the flask. Alternatingcurrent was run through the halogen bulb by application of 90 V using avariac connected to 110 V line power. Within seconds, an aerosolappeared and was drawn into the 1 L flask by use of the piston, withformation of the aerosol terminated after 6 s. The aerosol was allowedto sediment onto the walls of the 1 L flask for approximately 30minutes. The flask was then extracted with acetonitrile and the extractanalyzed by HPLC with detection by light absorption at 225 nm.Comparison with standards containing known amounts of pergolide revealedthat 0.3 mg of >99% pure pergolide had been collected in the flask,resulting in an aerosol drug mass density of 0.3 mg/L. The aluminum foilupon which the pergolide had previously been coated was weighedfollowing the experiment. Of the 1.0 mg originally coated on thealuminum, 1.0 mg of the material was found to have aerosolized in the 6s time period, implying a rate of drug aerosol formation of 0.2 mg/s.

1. A method of treating parkinsons disease comprising administering atherapeutic amount of a benzotropine, pergolide, ropinerole, anamtadineor deprenyl condensation aerosol, having an MMAD less than 3 μm and lessthan 5% benzotropine, pergolide, ropinerole, anamtadine or deprenyldegradation products, to a patient by inhalation, upon activation by thepatient of the formation of, and delivery of, the condensation aerosol.2. The method of claim 1, wherein said condensation aerosol is formed bya. volatilizing benzotropine, pergolide, ropinerole, anamtadine ordeprenyl under conditions effective to produce a heated vapor of thebenzotropine, pergolide, ropinerole, anamtadine or deprenyl, and b.condensing the heated vapor of the benzotropine, pergolide, ropinerole,anamtadine or deprenyl to form condensation aerosol particles.
 3. Themethod according to claim 1, wherein the condensation aerosol is formedat a rate greater than 0.5 mg/second.
 4. The method according to claim1, wherein said therapeutic amount of benzotropine condensation aerosolcomprises between 0.1 mg and 4 mg of benzotropine delivered in a singleinspiration.
 5. The method according to claim 1, wherein saidtherapeutic amount of pergolide condensation aerosol comprises between0.01 mg and 2.5 mg of pergolide delivered in a single inspiration. 6.The method according to claim 1, wherein said therapeutic amount ofropinerole condensation aerosol comprises between 0.02 mg and 4 mg ofropinerole delivered in a single inspiration.
 7. The method according toclaim 1 wherein said therapeutic amount of anamtadine condensationaerosol comprises between 5 mg and 500 mg of anamtadine delivered in asingle inspiration.
 8. The method according to claim 1 wherein saidtherapeutic amount of deprenyl condensation aerosol comprises between0.5 mg and 12.5 mg of deprenyl delivered in a single inspiration.
 9. Themethod according to claim 2, wherein said administration results in apeak plasma concentration of said benzotropine, pergolide, ropinerole,anamtadine or deprenyl in less than 0.1 hours.
 10. The method accordingto claim 1, wherein at least 50% by weight of the condensation aerosolis amorphous in form.
 11. A method of administering benzotropine,pergolide, ropinerole, anamtadine or deprenyl to a patient to achieve apeak plasma drug concentration rapidly, comprising administering to thepatient by inhalation an aerosol of benzotropine, pergolide, ropinerole,anamtadine or deprenyl having less than 5% benzotropine, pergolide,ropinerole, anamtadine or deprenyl degradation products and an MMAD lessthan 3 microns wherein the peak plasma drug concentration is achieved inless than 0.1 hours.
 12. A kit for delivering a drug aerosol comprising:a) a thin coating of an benzotropine, pergolide, ropinerole, anamtadineor deprenyl composition, and b) a device for dispensing said thincoating as a condensation aerosol.
 13. The kit of claim 12, wherein thedevice for dispensing said coating as a condensation aerosol comprises:(a) a flow through enclosure, (b) contained within the enclosure, ametal substrate with a foil-like surface and having a thin coating ofbenzotropine, pergolide, ropinerole, anamtadine or deprenyl compositionformed on the substrate surface, (c) a power source that can beactivated to heat the substrate to a temperature effective to volatilizethe benzotropine, pergolide, ropinerole, anamtadine or deprenylcomposition contained in said coating, and (d) inlet and exit portalsthrough which air can be drawn through said device by inhalation,wherein heating the substrate by activation of the power source iseffective to form a benzotropine, pergolide, ropinerole, anamtadine ordeprenyl vapor containing less than 5% benzotropine, pergolide,ropinerole, anamtadine or deprenyl degradation products, and drawing airthrough said chamber is effective to condense the benzotropine,pergolide, ropinerole, anamtadine or deprenyl vapor to form aerosolparticles wherein the aerosol has an MMAD of less than 3 microns. 14.The kit according to claim 13, wherein the heat for heating thesubstrate is generated by an exothermic chemical reaction.
 15. The kitaccording to claim 14, wherein said exothermic chemical reaction isoxidation of combustible materials.
 16. The kit according to claim 13,wherein the heat for heating the substrate is generated by passage ofcurrent through an electrical resistance element.
 17. The kit accordingto claim 13, wherein said substrate has a surface area dimensioned toaccommodate a therapeutic dose of benzotropine, pergolide, ropinerole,anamtadine or deprenyl composition in said coating.
 18. The kitaccording to claim 12, wherein a peak plasma concentration ofbenzotropine, pergolide, ropinerole, anamtadine or deprenyl is obtainedin less than 0.1 hours after delivery of condensation aerosol to thepulmonary system.
 19. The kit of claim 12, further includinginstructions for use.